a study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations in patients with metastatic colorectal cancer (morpheus-crc)

Conditions: Colorectal Cancer

Summary: a phase ib/ii, open-label, multicenter, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with metastatic colorectal cancer (mcrc) that became refractory to first- and second-line standard therapies. eligible patients will be assigned to one of several treatment arms.


Eligibility criteria:
inclusion criteria: * eastern cooperative oncology group (ecog) performance status of 0 or 1 * life expectancy ≥ 3 months, as determined by the investigator * histologically confirmed adenocarcinoma originating from the colon or rectum * metastatic disease not amenable to local treatment * disease progression during or following not more than two separate lines of treatment for metastatic colorectal cancer (mcrc) that consisted of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy in combination with a biologic agent * measurable disease (at least one target lesion) according to recist v1.1 * adequate hematologic and end-organ function obtained within 14 days prior to initiation of study treatment exclusion criteria: * high microsatellite instability (msi-h) tumor * presence of brafv600e mutation * prior treatment with any of the protocol-specified study treatments * prior treatment with t-cell co-stimulating or immune checkpoint blockade therapies including anti-ctla-4, anti-pd-1, and anti-pd-l1 therapeutic antibodies * biologic treatment within 2 weeks prior to initiation of study treatment, or other systemic treatment for crc within 2 weeks or 5 half-lives of the drug (whichever is shorter) prior to initiation of study treatment * treatment with investigational therapy within 28 days prior to initiation of study treatment * eligibility only for the control arm * prior allogeneic stem cell or solid organ transplantation * treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to the initiation of study treatment * treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment * treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab * current treatment with anti-viral therapy for hbv * uncontrolled pleural effusion, pericardial effusion, ascites requiring recurrent drainage procedures (once monthly or more frequently), or tumor related-pain, * uncontrolled or symptomatic hypercalcemia (ionized calcium \>1.5 mmol/l, calcium \>12 mg/dl, or corrected serum calcium \>uln) * symptomatic, untreated, or actively progressing cns metastases * history of leptomeningeal disease * active or history of autoimmune disease or immune deficiency * history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (ct) scan * history of malignancy other than crc within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death * active tuberculosis * severe infection within 4 weeks prior to initiation of study treatment * significant cardiovascular disease * grade ≥3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment * major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study * history of severe allergic reactions to chimeric or humanized antibodies or fusion proteins * inability to swallow medications * malabsorption condition that would alter the absorption of orally administered medications * evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding * urine dipstick ≥ 2+ protein or ≥ 3.5 g of protein in a 24-hour urine collection